Emerging roles of post-translational modifications in signal transduction and angiogenesis

Proteomics. 2015 Jan;15(2-3):300-9. doi: 10.1002/pmic.201400183. Epub 2014 Oct 8.

Abstract

The vascular endothelial growth factor receptor-2 (VEGFR-2) belongs to the family of receptor tyrosine kinases and is a key player in vasculogenesis and pathological angiogenesis. An emerging picture of PTMs of VEGFR-2 suggests that they play central roles in generating a highly dynamic and complex signaling system that regulates key angiogenic responses ranging from endothelial cell differentiation, proliferation, migration to permeability. Recent MS analysis of VEGFR-2 uncovered previously unrecognized PTMs on VEGFR-2 with a distinct function. The ligand binding extracellular domain of VEGFR-2 is composed of seven immunoglobulin-like domains highly decorated with N-glycosylation, while its cytoplasmic domain is subject to multiple PTMs including Tyr, Ser/Thr phosphorylation, Arg and Lys methylation, acetylation and ubiquitination. Here we review the PTMs on VEGFR-2, their importance in angiogenic signaling relays and possible novel therapeutic potentials.

Keywords: Acetylation; Cell biology; Glycosylation; Phosphorylation; Tandem mass spectrometry; VEGF receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Glycosylation
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Physiologic*
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Signal Transduction*
  • Vascular Endothelial Growth Factor Receptor-2 / analysis
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Vascular Endothelial Growth Factor Receptor-2